The objective of this study is to elucidate the cellular and molecular mechanisms of neoplastic development and to understand how environmental agents influence the progression of normal cells to malignancy. The specific aims of the research are: (1) to determine whether carcinogen induced mutations are important in carcinogenesis; (2) to determine the nature of critical carcinogen induced genetic changes (i.e., whether they are gene mutations, chromosomal aberrations or rearrangements, or numerical changes in chromosomes); (3) to understand the mechanism of action of certain environmental carcinogens which are possibly nonelectrophilic (e.g., diethylstilbestrol, asbestos and nickel; and (4) to determine the mechanism by which tumor promoters enhance or induce cell transformation.